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Researchers Pinpoint Novel Gene-Environment Interaction in Cells from People with MS

June 2, 2011

Studying human cells isolated in the laboratory, researchers reveal a novel interaction between two genes that influence susceptibility to developing MS, certain environmental factors, and a chemical process (called N-glycosylation) that modifies the structure of molecules, which together may contribute to our understanding of how complex interactions lead to the development of MS. Michael Demetriou, MD, PhD (University of California, Irvine) and colleagues have published these findings in Nature Communications (May 31, 2011, Volume 2, Article #334). The team was funded in part by the National MS Society.

Background: The cause of MS is still not known, but scientists believe that a combination of several factors may be involved to trigger the immune attack that is launched on the brain and spinal cord. While MS is not directly inherited, genes are known to make people susceptible to developing the disease. Researchers also are working to understand how MS gene variations may interact with some environmental triggers that have been linked to MS, such as viral infection, cigarette smoking and low levels of vitamin D/sunlight to increase the risk of MS.

Michael Demetriou, MD, PhD, has previously shown that changes in the addition of specific sugars to proteins involved in the MS attack (N-glycosylation) trigger a spontaneous MS-like disease in mice, which could be suppressed by interfering with the process with a dietary supplement. The current study aimed at translating this finding to the development of human disease.

The Study: In this study, Dr. Demetriou’s team examined DNA samples from about 13,000 people with MS or controls. They looked at how four previously reported susceptibility genes that are involved in immune system activities (interleukin-7 receptor-alpha, interleukin-2 receptor-alpha, MGAT1 and CTLA-4) affect N-glycosylation. Then they examined how a particular environmental factor such as vitamin D affected this interaction.

The results suggest that these genes do alter N-glycosylation in cells isolated in the laboratory, but that both vitamin D and a dietary supplement called N-acetylglucosamine (GlcNAc) were able to suppress this process in cells and in mouse models of MS.

Comment: This study provides new evidence for a link between genes and the environment in the development of MS. However, additional research is needed before it is possible to generalize these findings to all cases of MS, since this study focused on just a few of the many genetic susceptibility factors linked to MS. More research is also needed to determine whether administering vitamin D and G1cNAc will be helpful in MS. A new clinical trial getting underway with support from the National MS Society will test the ability of vitamin D supplements to alter MS disease activity.

Watch a webcast on the range of ongoing efforts to find the cause and cure for MS, “Who? Why? How? - Searching for the Cause of Multiple Sclerosis.”

About Multiple Sclerosis

Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.